A study of oligosaccharide variants of alpha‐fetoproteins produced by normal fetuses and fetuses with trisomy 21

Yamamoto, Ritsu; Ohkouchi, Toshihiro; Tabata, Kouichi; Ebina, Yasuhiko; Watari, Hidemichi; Kudo, Masataka; Shimizu, Kayoko; Satomura, Shinji; Minakami, Hisanori; Sakuragi, Noriaki

doi:10.1111/j.0001-6349.2005.00815.x

Cited by 6 publications

(3 citation statements)

References 19 publications

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“…AFP-L3 is predominantly found in the serum of mothers of children with DS -its transplacental passage is probably promoted relative to the other 2 isoforms. It was later proven that the use of AFP-L3 instead of AFP increases the sensitivity of the triple test [13,14], while the use of AFP-L2 and AFP-L3 improves the detectability of open neural tube defects and abdominal wall defects [15]. AFP-L3 is the predominant isoform of AFP found in hepatocellular carcinoma based on hepatic cirrhosis and hepatitis [3].…”

Section: Mrna Variants and Isoforms Of Afpmentioning

confidence: 99%

Alpha-fetoprotein (AFP) — new aspects of a well-known marker in perinatology

Głowska-Ciemny¹,

Pankiewicz²,

Malewski

et al. 2022

Ginekol Pol

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Alpha-fetoprotein (AFP) is a serum protein, which is characteristic of the fetal development period and a well-known oncological marker. The predominance of AFP among serum proteins is common in fetal life, whereas after birthing its functions are gradually taken over by albumins. An understanding of the mechanism of AFP transfer between fetus and mother has led to the development of screening tests for identifying neural tube defects and Down's syndrome. Currently, the knowledge on patophysiology and the possible importance of AFP in perinatology and fetal medicine extends far beyond those 2 disease states. Throughout the 50 years of research on AFP, there has been dynamic progress of diagnostic techniques, from the qualitative ones that are used solely for scientific studies to the widely used radioimmunoassays and immunoenzymatic assays (enzyme-linked immunosorbent assay, chemiluminescence immunoassay, time-resolved fluorescence immunoassay). Some genetic mutations cause complete inhibition of AFP production by the fetus. This affects the results of screening tests during pregnancy, and also leads to constantly high levels of AFP in adults, which are not linked to oncogenesis.

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Section: Mrna Variants and Isoforms Of Afpmentioning

confidence: 99%

Alpha-fetoprotein (AFP) — new aspects of a well-known marker in perinatology

Głowska-Ciemny¹,

Pankiewicz²,

Malewski

et al. 2022

Ginekol Pol

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“…Additionally, the maternal serum AFP level was decreased, which may be associated with specific AFP transport defects. Yamamoto et al [ 25 ] also confirmed that the placental AFP-L3 level in pregnant women carrying fetuses with trisomy 21 was elevated, which may explain the increased serum level of AFP-L3 in these women. Therefore, we speculate that the increased serum level of AFP-L2 in pregnant women carrying fetuses with trisomy 21 in early pregnancy is similar to that of AFP or AFP-L3.…”

Section: Discussionmentioning

confidence: 92%

A Risk Model for Predicting Fetuses with Trisomy 21 Using Alpha-Fetoprotein Variants L2 Combined with Maternal Serum Biomarkers in Early Pregnancy

Chen

Ning

et al. 2021

Reprod. Sci.

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To establish a risk prediction model and the clinical value of trisomy 21 using alpha-fetoprotein variants L2 (AFP-L2) combined with maternal serum biomarkers and nuchal translucency (NT) thickness in early pregnancy. A retrospective case–control study was conducted. The subjects were divided into the case group (n = 40) or the control group (n = 40). An enzyme-linked immunosorbent assay was used to measure the maternal serum AFP-L2 level in both groups. The AFP-L2 single-index or multi-index combined risk model was used to predict the efficiency of trisomy 21. The best cut-off value and area under the curve (AUC) were determined to evaluate the predictive efficacy of different risk models constructed by AFP-L2. The maternal serum AFP-L2 level in the case group was 1.59 (0.61–3.61) Multiple of medium (MoM), which was higher than 1.00 (0.39–2.12) MoM in the control group (P < 0.001). The free beta-human chorionic gonadotropin (free β-hCG) level and NT in the case group were significantly higher than those in the control group (P < 0.001). The pregnancy-associated plasma protein A (PAPP-A) level in the case group was lower than that in the control group (P < 0.001). The AUC of AFP-L2 in predicting trisomy 21 was 0.797. After considering the maternal serum AFP-L2 level, the AUC, detection rate (DR), positive predictive value (PPV), negative predictive value (NPV), falsepositive rate (FPR), false negative rate (FNR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were significantly improved. In this study, PAPP-A + free β-hCG + NT + AFP-L2 and PAPP-A + free β-hCG + AFP-L2 increased the integrated discrimination improvement (IDI) and net classification improvement (NRI) of predicting fetuses with trisomy 21 (1.10% and 5.27%; 11.07% and 2.78%) (1.10% and 5.27%; 11.07% and 2.78%), respectively, after considering the maternal serum AFP-L2 level. The maternal serum AFP-L2 level in early pregnancy had high sensitivity and specificity, and it was a good biomarker to predict fetuses with trisomy 21.

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“…Yamamoto et al posited that the placental transfer of the AFP-L3 component in women carrying a fetus with trisomy 21 may be relatively high, which might be one of the causes for the elevated serum AFP-L3 levels in these pregnant women 36 . In addition, Yamamoto 37 did not detect a correlation between maternal serum AFP-L3 and AFP MoMs (r = 0.006) and did not observe a significant correlation between serum AFP level and AFP-L3 percentage.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of maternal alpha-fetoprotein variants in second-trimester biochemical screening for trisomy 21 and 18

Chen

Ning

et al. 2022

Sci Rep

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To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15–20+6 weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer–lemeshow (H-L) test were used to investigate the predictive value of free β-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free β-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free β-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free β-hCG, followed by AFP-L2 + free β-hCG and AFP-L3 + free β-hCG, and finally AFP + free β-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free β-hCG is the best.

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A study of oligosaccharide variants of alpha‐fetoproteins produced by normal fetuses and fetuses with trisomy 21

Abstract: The transference of the AFP-L3 fraction might be relatively high in the placentas of women carrying a trisomy 21 fetus, and this could be the one of the reasons for the increase in the percentage of AFP-L3 in the maternal serum in pregnancies with a trisomy 21 fetus.

Cited by 6 publications

References 19 publications

Alpha-fetoprotein (AFP) — new aspects of a well-known marker in perinatology

Alpha-fetoprotein (AFP) — new aspects of a well-known marker in perinatology

A Risk Model for Predicting Fetuses with Trisomy 21 Using Alpha-Fetoprotein Variants L2 Combined with Maternal Serum Biomarkers in Early Pregnancy

Diagnostic value of maternal alpha-fetoprotein variants in second-trimester biochemical screening for trisomy 21 and 18

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